Metathesis is a catalytic reaction and involves the interchange of alkylidene units among olefinic hydrocarbons via the formation and cleavage of carbon-carbon double bonds. The metathesis reaction may occur between two of the same type of molecules, referred to as self-metathesis, and/or may occur between two dissimilar types of molecules, referred to as cross-metathesis. Metathesis is a well-known and useful synthetic step in the production of industrial chemicals.
Metathesis reactions are typically catalyzed by transition metal carbene complexes, for example, complexes comprising ruthenium, molybdenum, osmium, chromium, rhenium, or tungsten. Upon completion of the metathesis reaction it is typically desirable to remove at least a portion of the metathesis catalyst from the metathesis products.
In one known method for removing metathesis catalyst, tris-(hydroxymethyl)phosphine (THMP) is added to the metathesis products at a rate of about 25 to 100 mol equivalents THMP per mole of metathesis catalyst. The resulting mixture is then stirred at a temperature of about 60° C. to 70° C. for about 18 to 24 hours under inert atmosphere (e.g., N2 gas). Degassed water or methanol (e.g., about 150 mL per L of reaction mixture) is then added and stirred for about 10 minutes. The mixture is then centrifuged to provide phase separation. The THMP complexes with the metathesis catalyst allowing it to be removed by separation of the water or methanol phase.
In a variation to this method (see, Maynard and Grubbs, Tetrahedron 1999, 40, 4137-4140) triethylamine is added along with THMP to the metathesis products, followed by treatment with an excess of silica gel and filtration. A level of 206 ppm Ru in the product is reported.
In another reported method (see, Paquette et. al. Organic Letters 2000, 2(9), 1259-1261), 1.5 equivalents of lead tetraacetate is added to the reaction mixture and stirred overnight, followed by filtration through a pad of silica gel. A level of 300 ppm of Ru in the product is reported.
In another reported method (see, Ahn et. al.; Organic Letters 2001, 3(9), 1411-1413) 50 equivalents of triphenylphosphine oxide or dimethyl sulfoxide is added to the reaction mixture, followed by chromatography on silica gel. A level of 100 ppm Ru in the product is reported.
Other reported methods include the method of Cho and Kim (see, Organic Letters 2003, 5(4), 531-533) (reports treatment of the reaction mixture with silica and at least 50 equivalents of carbon, followed by column chromatography on silica gel. A level of 12 ppm Ru in the product is reported.); the method of Westhus et. al. (see, Tetrahedron Letters 2004, 45, 3141-3142) (reports the use of a polymer-bound chelate phosphine, optionally followed by treatment with silica gel or carbon. A level of 1120 to 2400 ppm is reported.); the method reported in WO 2003/026770 (reports the use of 360 equivalents of activated alumina, followed by filtration through Celite brand activated charcoal. A level of 9 ppm Ru in the final product is reported.); the method of WO 2005/056182 (reports the use of supercritical CO2 to precipitate the catalyst. A level of 56 ppm Ru in the final product is reported.); and the method reported in WO 2005/075502 (reports the use of dithiothreitol, dithioerythritol, or citric acid, followed by extraction with water and aqueous base, and finally treatment with charcoal. A level of 210 to 310 ppm Ru in the final product is reported.).
Often, metathesis is followed by hydrogenation, whereby at least a portion of the double bond(s) that are present in the metathesis products are converted to single bonds. When metathesis is followed by hydrogenation, the metathesis catalyst is conventionally removed after the metathesis reaction but before the hydrogenation reaction. Although the removal of catalyst can be accomplished using known methods, the catalyst removal process adds a step to the manufacturing process with an associated material cost, processing cost, and yield loss. What is desired is a method of removing the metathesis catalyst (or the transition metal of the metathesis catalyst) that can be accomplished without adding a processing step to the manufacturing route of a chemical compound.